Association between Oxidative Stress and Frailty in an Elderly German Population: Results from the ESTHER Cohort Study
Background: Oxidative stress (OS) and inflammatory biomarkers have been postulated to be important factors in the development of age-related diseases. While causes of frailty are complex and multidimensional based on the interaction of genetic, biological, physical, and environmental factors, the bi...
Gespeichert in:
| Veröffentlicht in: | Gerontology (Basel) 2015-01, Vol.61 (5), p.407-415 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 415 |
|---|---|
| container_issue | 5 |
| container_start_page | 407 |
| container_title | Gerontology (Basel) |
| container_volume | 61 |
| creator | Saum, Kai-Uwe Dieffenbach, Aida Karina Jansen, Eugène H.J.M. Schöttker, Ben Holleczek, Bernd Hauer, Klaus Brenner, Hermann |
| description | Background: Oxidative stress (OS) and inflammatory biomarkers have been postulated to be important factors in the development of age-related diseases. While causes of frailty are complex and multidimensional based on the interaction of genetic, biological, physical, and environmental factors, the biological basis of frailty has been difficult to establish. Objective: In this study, we aimed to assess the possible association between different OS and inflammatory biomarkers and frailty. Methods: This cross-sectional analysis was performed among 2,518 subjects participating in a large population-based cohort study on aging conducted in Germany. Frailty was assessed as proposed by Fried et al. [J Gerontol A Biol Sci Med Sci 2001;56:M146-M156]. OS biomarkers, biological antioxidant potential (BAP), derivate of reactive oxygen metabolites (d-ROM) and total thiol levels (TTL), and an established biomarker of inflammation C-reactive protein (CRP) were measured by spectrophotometry and immunoturbidimetry. Logistic regression models were performed to assess the relationship between the OS biomarkers and frailty status. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to quantify the associations. Results: Mean levels of d-ROM, TTL, and CRP differed between frail and non-frail participants (p values |
| doi_str_mv | 10.1159/000380881 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1159_000380881</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A637204637</galeid><sourcerecordid>A637204637</sourcerecordid><originalsourceid>FETCH-LOGICAL-c501t-337c83f3d3384ca2864a536acd65e9ba294ca824b4d1f7445d30fb4a8911c0ea3</originalsourceid><addsrcrecordid>eNpd0c9P2zAUB3ALgaAwDrtPkyUktB2y-WcSc6uq8kNCYgImcYuc-IUGnLjYDlv_-7lr18Mutt5XHz_begh9pOQbpVJ9J4TwkpQl3UMTKhjP1sE-mhBORMaZeDpCxyG8pJAwSg7REZOKiYKxCXqfhuCaTsfODbiG-AtgwHe_O5OSd8AP0UMIWA8GX3rd2bjC3ZBKPLcGvF3hK_B9Kn-45Wj_NrnA9xBGGwNuvetxXACePzxez-_xzC2cj6nlaFYf0EGrbYDT7X6Cfl7OH2fX2e3d1c1seps1ktCYcV40JW-54bwUjWZlLrTkuW5MLkHVmqmUlkzUwtC2EEIaTtpa6FJR2hDQ_AR92fRdevc2QohV34UGrNUDuDFUtCCFlFxRmejZf_TFjX5Ir0uKF0oxpvKkzjfqWVuoFqBtXARnx_XXQzXNecGISGuCXzew8S4ED2219F2v_aqipFpPrdpNLdnP26vHugezk__GlMCnDXjV_hn8DmzP_wHb25kq</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1737992296</pqid></control><display><type>article</type><title>Association between Oxidative Stress and Frailty in an Elderly German Population: Results from the ESTHER Cohort Study</title><source>MEDLINE</source><source>Karger Journals</source><source>Alma/SFX Local Collection</source><creator>Saum, Kai-Uwe ; Dieffenbach, Aida Karina ; Jansen, Eugène H.J.M. ; Schöttker, Ben ; Holleczek, Bernd ; Hauer, Klaus ; Brenner, Hermann</creator><creatorcontrib>Saum, Kai-Uwe ; Dieffenbach, Aida Karina ; Jansen, Eugène H.J.M. ; Schöttker, Ben ; Holleczek, Bernd ; Hauer, Klaus ; Brenner, Hermann</creatorcontrib><description>Background: Oxidative stress (OS) and inflammatory biomarkers have been postulated to be important factors in the development of age-related diseases. While causes of frailty are complex and multidimensional based on the interaction of genetic, biological, physical, and environmental factors, the biological basis of frailty has been difficult to establish. Objective: In this study, we aimed to assess the possible association between different OS and inflammatory biomarkers and frailty. Methods: This cross-sectional analysis was performed among 2,518 subjects participating in a large population-based cohort study on aging conducted in Germany. Frailty was assessed as proposed by Fried et al. [J Gerontol A Biol Sci Med Sci 2001;56:M146-M156]. OS biomarkers, biological antioxidant potential (BAP), derivate of reactive oxygen metabolites (d-ROM) and total thiol levels (TTL), and an established biomarker of inflammation C-reactive protein (CRP) were measured by spectrophotometry and immunoturbidimetry. Logistic regression models were performed to assess the relationship between the OS biomarkers and frailty status. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to quantify the associations. Results: Mean levels of d-ROM, TTL, and CRP differed between frail and non-frail participants (p values <0.0001). Comparing highest and lowest quartiles of the biomarkers, statistically significant positive associations with frailty were observed for d-ROM (OR: 2.02, 95% CI: 1.25-3.25) and CRP (OR: 3.15, 95% CI: 2.00-4.96), respectively, after controlling for age and sex. An inverse statistically significant association with frailty was observed for TTL (OR: 0.42, 95% CI: 0.25-0.69). Conclusion: The strong associations with OS biomarkers and CRP support a major role of OS and inflammation in the development of frailty, which should be followed up in further longitudinal studies on frailty.</description><identifier>ISSN: 0304-324X</identifier><identifier>EISSN: 1423-0003</identifier><identifier>DOI: 10.1159/000380881</identifier><identifier>PMID: 25924722</identifier><language>eng</language><publisher>Basel, Switzerland: S. Karger AG</publisher><subject>Aged ; Aged, 80 and over ; Aging ; Biological markers ; Biomarkers ; Biomarkers - blood ; C-Reactive Protein - metabolism ; Clinical Section / Original Paper ; Cohort Studies ; Cross-Sectional Studies ; Development and progression ; Diagnosis ; Female ; Frail Elderly ; Frailty ; Free radicals ; Germany ; Gerontology ; Health aspects ; Humans ; Inflammation ; Inflammation Mediators - blood ; Logistic Models ; Male ; Oxidative Stress ; Reactive Oxygen Species - blood ; Statistics ; Sulfhydryl Compounds - blood</subject><ispartof>Gerontology (Basel), 2015-01, Vol.61 (5), p.407-415</ispartof><rights>2015 S. Karger AG, Basel</rights><rights>COPYRIGHT 2015 S. Karger AG</rights><rights>Copyright S. Karger AG Aug 2015</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c501t-337c83f3d3384ca2864a536acd65e9ba294ca824b4d1f7445d30fb4a8911c0ea3</citedby><cites>FETCH-LOGICAL-c501t-337c83f3d3384ca2864a536acd65e9ba294ca824b4d1f7445d30fb4a8911c0ea3</cites><orcidid>0000-0001-8041-5705 ; 0000-0002-1217-4521</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2429,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25924722$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Saum, Kai-Uwe</creatorcontrib><creatorcontrib>Dieffenbach, Aida Karina</creatorcontrib><creatorcontrib>Jansen, Eugène H.J.M.</creatorcontrib><creatorcontrib>Schöttker, Ben</creatorcontrib><creatorcontrib>Holleczek, Bernd</creatorcontrib><creatorcontrib>Hauer, Klaus</creatorcontrib><creatorcontrib>Brenner, Hermann</creatorcontrib><title>Association between Oxidative Stress and Frailty in an Elderly German Population: Results from the ESTHER Cohort Study</title><title>Gerontology (Basel)</title><addtitle>Gerontology</addtitle><description>Background: Oxidative stress (OS) and inflammatory biomarkers have been postulated to be important factors in the development of age-related diseases. While causes of frailty are complex and multidimensional based on the interaction of genetic, biological, physical, and environmental factors, the biological basis of frailty has been difficult to establish. Objective: In this study, we aimed to assess the possible association between different OS and inflammatory biomarkers and frailty. Methods: This cross-sectional analysis was performed among 2,518 subjects participating in a large population-based cohort study on aging conducted in Germany. Frailty was assessed as proposed by Fried et al. [J Gerontol A Biol Sci Med Sci 2001;56:M146-M156]. OS biomarkers, biological antioxidant potential (BAP), derivate of reactive oxygen metabolites (d-ROM) and total thiol levels (TTL), and an established biomarker of inflammation C-reactive protein (CRP) were measured by spectrophotometry and immunoturbidimetry. Logistic regression models were performed to assess the relationship between the OS biomarkers and frailty status. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to quantify the associations. Results: Mean levels of d-ROM, TTL, and CRP differed between frail and non-frail participants (p values <0.0001). Comparing highest and lowest quartiles of the biomarkers, statistically significant positive associations with frailty were observed for d-ROM (OR: 2.02, 95% CI: 1.25-3.25) and CRP (OR: 3.15, 95% CI: 2.00-4.96), respectively, after controlling for age and sex. An inverse statistically significant association with frailty was observed for TTL (OR: 0.42, 95% CI: 0.25-0.69). Conclusion: The strong associations with OS biomarkers and CRP support a major role of OS and inflammation in the development of frailty, which should be followed up in further longitudinal studies on frailty.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Aging</subject><subject>Biological markers</subject><subject>Biomarkers</subject><subject>Biomarkers - blood</subject><subject>C-Reactive Protein - metabolism</subject><subject>Clinical Section / Original Paper</subject><subject>Cohort Studies</subject><subject>Cross-Sectional Studies</subject><subject>Development and progression</subject><subject>Diagnosis</subject><subject>Female</subject><subject>Frail Elderly</subject><subject>Frailty</subject><subject>Free radicals</subject><subject>Germany</subject><subject>Gerontology</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Inflammation Mediators - blood</subject><subject>Logistic Models</subject><subject>Male</subject><subject>Oxidative Stress</subject><subject>Reactive Oxygen Species - blood</subject><subject>Statistics</subject><subject>Sulfhydryl Compounds - blood</subject><issn>0304-324X</issn><issn>1423-0003</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpd0c9P2zAUB3ALgaAwDrtPkyUktB2y-WcSc6uq8kNCYgImcYuc-IUGnLjYDlv_-7lr18Mutt5XHz_begh9pOQbpVJ9J4TwkpQl3UMTKhjP1sE-mhBORMaZeDpCxyG8pJAwSg7REZOKiYKxCXqfhuCaTsfODbiG-AtgwHe_O5OSd8AP0UMIWA8GX3rd2bjC3ZBKPLcGvF3hK_B9Kn-45Wj_NrnA9xBGGwNuvetxXACePzxez-_xzC2cj6nlaFYf0EGrbYDT7X6Cfl7OH2fX2e3d1c1seps1ktCYcV40JW-54bwUjWZlLrTkuW5MLkHVmqmUlkzUwtC2EEIaTtpa6FJR2hDQ_AR92fRdevc2QohV34UGrNUDuDFUtCCFlFxRmejZf_TFjX5Ir0uKF0oxpvKkzjfqWVuoFqBtXARnx_XXQzXNecGISGuCXzew8S4ED2219F2v_aqipFpPrdpNLdnP26vHugezk__GlMCnDXjV_hn8DmzP_wHb25kq</recordid><startdate>20150101</startdate><enddate>20150101</enddate><creator>Saum, Kai-Uwe</creator><creator>Dieffenbach, Aida Karina</creator><creator>Jansen, Eugène H.J.M.</creator><creator>Schöttker, Ben</creator><creator>Holleczek, Bernd</creator><creator>Hauer, Klaus</creator><creator>Brenner, Hermann</creator><general>S. Karger AG</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>0-V</scope><scope>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>88J</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ALSLI</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M2P</scope><scope>M2R</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>S0X</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-8041-5705</orcidid><orcidid>https://orcid.org/0000-0002-1217-4521</orcidid></search><sort><creationdate>20150101</creationdate><title>Association between Oxidative Stress and Frailty in an Elderly German Population: Results from the ESTHER Cohort Study</title><author>Saum, Kai-Uwe ; Dieffenbach, Aida Karina ; Jansen, Eugène H.J.M. ; Schöttker, Ben ; Holleczek, Bernd ; Hauer, Klaus ; Brenner, Hermann</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c501t-337c83f3d3384ca2864a536acd65e9ba294ca824b4d1f7445d30fb4a8911c0ea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Aging</topic><topic>Biological markers</topic><topic>Biomarkers</topic><topic>Biomarkers - blood</topic><topic>C-Reactive Protein - metabolism</topic><topic>Clinical Section / Original Paper</topic><topic>Cohort Studies</topic><topic>Cross-Sectional Studies</topic><topic>Development and progression</topic><topic>Diagnosis</topic><topic>Female</topic><topic>Frail Elderly</topic><topic>Frailty</topic><topic>Free radicals</topic><topic>Germany</topic><topic>Gerontology</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Inflammation Mediators - blood</topic><topic>Logistic Models</topic><topic>Male</topic><topic>Oxidative Stress</topic><topic>Reactive Oxygen Species - blood</topic><topic>Statistics</topic><topic>Sulfhydryl Compounds - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Saum, Kai-Uwe</creatorcontrib><creatorcontrib>Dieffenbach, Aida Karina</creatorcontrib><creatorcontrib>Jansen, Eugène H.J.M.</creatorcontrib><creatorcontrib>Schöttker, Ben</creatorcontrib><creatorcontrib>Holleczek, Bernd</creatorcontrib><creatorcontrib>Hauer, Klaus</creatorcontrib><creatorcontrib>Brenner, Hermann</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Social Sciences Premium Collection</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>Social Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Social Science Premium Collection</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Science Database</collection><collection>Social Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><jtitle>Gerontology (Basel)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Saum, Kai-Uwe</au><au>Dieffenbach, Aida Karina</au><au>Jansen, Eugène H.J.M.</au><au>Schöttker, Ben</au><au>Holleczek, Bernd</au><au>Hauer, Klaus</au><au>Brenner, Hermann</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association between Oxidative Stress and Frailty in an Elderly German Population: Results from the ESTHER Cohort Study</atitle><jtitle>Gerontology (Basel)</jtitle><addtitle>Gerontology</addtitle><date>2015-01-01</date><risdate>2015</risdate><volume>61</volume><issue>5</issue><spage>407</spage><epage>415</epage><pages>407-415</pages><issn>0304-324X</issn><eissn>1423-0003</eissn><abstract>Background: Oxidative stress (OS) and inflammatory biomarkers have been postulated to be important factors in the development of age-related diseases. While causes of frailty are complex and multidimensional based on the interaction of genetic, biological, physical, and environmental factors, the biological basis of frailty has been difficult to establish. Objective: In this study, we aimed to assess the possible association between different OS and inflammatory biomarkers and frailty. Methods: This cross-sectional analysis was performed among 2,518 subjects participating in a large population-based cohort study on aging conducted in Germany. Frailty was assessed as proposed by Fried et al. [J Gerontol A Biol Sci Med Sci 2001;56:M146-M156]. OS biomarkers, biological antioxidant potential (BAP), derivate of reactive oxygen metabolites (d-ROM) and total thiol levels (TTL), and an established biomarker of inflammation C-reactive protein (CRP) were measured by spectrophotometry and immunoturbidimetry. Logistic regression models were performed to assess the relationship between the OS biomarkers and frailty status. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to quantify the associations. Results: Mean levels of d-ROM, TTL, and CRP differed between frail and non-frail participants (p values <0.0001). Comparing highest and lowest quartiles of the biomarkers, statistically significant positive associations with frailty were observed for d-ROM (OR: 2.02, 95% CI: 1.25-3.25) and CRP (OR: 3.15, 95% CI: 2.00-4.96), respectively, after controlling for age and sex. An inverse statistically significant association with frailty was observed for TTL (OR: 0.42, 95% CI: 0.25-0.69). Conclusion: The strong associations with OS biomarkers and CRP support a major role of OS and inflammation in the development of frailty, which should be followed up in further longitudinal studies on frailty.</abstract><cop>Basel, Switzerland</cop><pub>S. Karger AG</pub><pmid>25924722</pmid><doi>10.1159/000380881</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-8041-5705</orcidid><orcidid>https://orcid.org/0000-0002-1217-4521</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0304-324X |
| ispartof | Gerontology (Basel), 2015-01, Vol.61 (5), p.407-415 |
| issn | 0304-324X 1423-0003 |
| language | eng |
| recordid | cdi_crossref_primary_10_1159_000380881 |
| source | MEDLINE; Karger Journals; Alma/SFX Local Collection |
| subjects | Aged Aged, 80 and over Aging Biological markers Biomarkers Biomarkers - blood C-Reactive Protein - metabolism Clinical Section / Original Paper Cohort Studies Cross-Sectional Studies Development and progression Diagnosis Female Frail Elderly Frailty Free radicals Germany Gerontology Health aspects Humans Inflammation Inflammation Mediators - blood Logistic Models Male Oxidative Stress Reactive Oxygen Species - blood Statistics Sulfhydryl Compounds - blood |
| title | Association between Oxidative Stress and Frailty in an Elderly German Population: Results from the ESTHER Cohort Study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T10%3A01%3A36IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Association%20between%20Oxidative%20Stress%20and%20Frailty%20in%20an%20Elderly%20German%20Population:%20Results%20from%20the%20ESTHER%20Cohort%20Study&rft.jtitle=Gerontology%20(Basel)&rft.au=Saum,%20Kai-Uwe&rft.date=2015-01-01&rft.volume=61&rft.issue=5&rft.spage=407&rft.epage=415&rft.pages=407-415&rft.issn=0304-324X&rft.eissn=1423-0003&rft_id=info:doi/10.1159/000380881&rft_dat=%3Cgale_cross%3EA637204637%3C/gale_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1737992296&rft_id=info:pmid/25924722&rft_galeid=A637204637&rfr_iscdi=true |